In our previous grants, we have developed COG1410, a novel anti-inflammatory peptide with additional neuroprotective properties, for the treatment of Traumatic Brain Injury (TBI). Each year, TBI accounts for 50,000 deaths in the United States and of the 1,000,000 Americans treated and released from the Emergency Health Facilities, 230,000 survivors are disabled to the point that they will require significant care for the rest of their lives. In animal models of open and closed TBI, COG1410 was given 2 hours following the injury. Subsequent performance of COG1410 treated animals was significantly improved compared to controls on tests of balance, coordination, motor control, learning and memory. Based on the success in animals, our clinical goal is to intervene with a drug therapy in TBI patients that would lessen the severity of the response to TBI and thereby improve outcomes, like being capable of normal and independent activities of daily living without external assistance. This application is to perform all of the safety and toxicity studies required by the Food and Drug Administration (FDA) for submission and approval of an Investigational New Drug (IND) application for COG1410. In overview, we are required to synthesize high-quality COG1410 and use Good Laboratory Practices (GLP) methods to analyze COG1410 in different matrices, measure pharmacokinetics (PK) and toxicokinetics (TK) in rats and dogs using different amounts of COG1410 via intravenous injection and assess the safety of COG1410 in rats and dogs. Additional studies required of the IND are also detailed. The overall goal of this application is the successful completion of all studies, regulatory report submissions and necessary approvals that are needed to begin Phase 1 clinical trials of COG1410 in humans. PUBLIC HEALTH RELEVANCE: We have developed COG1410, a novel anti-inflammatory peptide with additional neuroprotective properties, for the treatment of Traumatic Brain Injury (TBI). Each year, TBI accounts for 50,000 deaths in the United States and of the 1,000,000 Americans treated and released from the Emergency Health Facilities, 230,000 survivors are disabled to the point that they will require significant care for the rest of their lives. Currently, there are no FDA approved treatments for Traumatic Brain Injury and the focus of this application is to bring COG1410, an investigational new drug that does protect animals from TBI, to human clinical trials and to human TBI patients.